Brazilian Society of Surgical Oncology recommendations on Merkel cell carcinoma surgical treatment.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer with poor 5-year survival rates. Surgery and radiation are the current first-line treatments for local and nodal disease. OBJECTIVES: The Brazilian Society of Surgical Oncology developed this document aiming to guide the surgical oncology role in multimodal MCC management. METHODS: The consensus was established in three rounds of online discussion, achieving consensus on specific topics including diagnosis, staging, treatment, and follow-up. RESULTS: Patients suspected of having MCC should undergo immunohistochemical examination and preferably undergo pathology review by a dermatopathologist. Initial staging should be performed with dermatologic and nodal physical examination, combined with complementary imaging. Whole-body imaging, preferably with positron emission tomography (PET) or computed tomography (CT) scans, are recommended. Due to the need for multidisciplinary approaches, we recommend that all cases should be discussed in tumor boards and referred to other specialties as soon as possible, reducing potential treatment delays. We recommend that all patients with clinical stage I or II may undergo local excision associated with sentinel lymph node biopsy. The decision on margin size should consider time to recovery, patient's comorbidities, and risk factors. Patients with positive sentinel lymph nodes or the presence of risk factors should undergo postoperative radiation therapy at the primary site. Exclusive radiation is a viable option for patients with low performance. Patients with positive sentinel lymph node biopsy should undergo nodal radiation therapy or lymphadenectomy. In patients with nodal clinical disease, in addition to primary tumor treatment, nodal radiation therapy and/or lymphadenectomy are recommended. Patients with advanced disease should preferably be enrolled in clinical trials and discussed in multidisciplinary meetings. The role of surgery and radiation therapy in the metastatic/advanced setting should be discussed individually and always in tumor boards. CONCLUSION: This document aims to standardize a protocol for initial assessment and treatment for Merkel cell carcinoma, optimizing oncologic outcomes in middle-income countries such as Brazil.

Recurrence Patterns and Clinical Management after a Positive Sentinel Node Biopsy in Melanoma Patients.

Introduction melanoma patients who become stage III after a positive sentinel node biopsy (SNB) may have several patterns of recurrence patients and methods retrospective analysis of melanoma patients who have undergone SNB in a single institution from 2000 to 2015. Results There were 111 recurrences (45.1%) among 246 (20.3%) SNB positive patients and median DRFS was 77.7 months. After initial treatment, further recurrences occurred in 68 (77.3%) patients, regardless the site of initial recurrence conclusions multimodal strategies are recommended to achieve better results when managing stage III melanoma patients after a positive SNB.

Local therapy in advanced melanoma after immune checkpoint inhibitors aiming to achieve complete response.

Background and Objectives: New scenarios for local therapy have arisen after starting immune checkpoint inhibitors (ICIs) to treat advanced melanoma (AM). The aim of this study is to examine the role of local therapies with curative intention for patients with AM that have been on ICI. Methods: This was a single institution, retrospective analysis of unresectable stage III or IV melanoma patients on treatment with anti-PD1 ± anti-CTLA-4 who underwent local therapy with curative intention with no other remaining sites of disease (NRD). Results: Of the 170 patients treated with ICI, 19 (11.2%) met the criteria of curative intention. The median time on ICI before local therapy was 16.6 months (range: 0.92-43.2). At the time of the local treatment, the disease was controlled in 16 (84.25%) and progressing in 3 patients (15.75%); 14 patients (73.7%) treated a single lesion and 5 (26.3%) treated 2 to 3 lesions. In a median follow-up of 17 months (range: 1.51-38.2) after the local therapy and 9.8 months after the last ICI cycle (range: 0.56-31), only 2 (10.5%) out of 19 patients relapsed. Conclusions: Patients with AM on treatment with ICI were able to achieve NRD after local treatment and may benefit from long-term disease control without systemic treatment.

Multiple Primary Melanoma: A Five-Year Prospective Single-Center Follow-Up Study of Two MC1R R/R Genotype Carriers.

BACKGROUND: Multiple primary melanoma (MPM) is a diagnostic challenge even with ancillary imaging technologies available to dermatologists. In selected patients' phenotypes, the use of imaging approaches can help better understand lesion characteristics, and aid in early diagnosis and management. METHODS: Under a 5-year prospective single-center follow-up, 58 s primary melanomas (SPMs) were diagnosed in two first-degree relatives, with fair skin color, red hair, green eyes, and personal history of one previous melanoma each. Patients' behavior and descriptive demographic data were collected from medical records. The information on the first two primary melanomas (PMs) were retrieved from pathology reports. The characteristics of 60 melanomas were collected from medical records, video dermoscopy software, and pathology reports. Reflectance confocal microscopy (RCM) was performed prior to excision of 22 randomly selected melanomas. RESULTS: From February 2018 to May 2023, two patients underwent a pooled total of 214 excisional biopsies of suspect lesions, resulting in a combined benign versus malignant treatment ratio (NNT) of 2.0:1.0. The number of moles excised for each melanoma diagnosed (NNE) was 1.7:1.0 and 6.9:1.0 for the female and male patient respectively. The in-situ melanoma/invasive melanoma ratio (IIR) demonstrated a higher proportion of in-situ melanomas for both patients. From June 2018 to May 2023, a total of 58 SPMs were detected by the combination of total body skin exam (TBSE), total body skin photography (TBSP), digital dermoscopy (DD), and sequential digital dermoscopy imaging (SDDI) via comparative approach. The younger patient had her PM one month prior to the second and third cutaneous melanomas (CMs), characterizing a case of synchronous primary CM. The male older relative had a total of 7 nonsynchronous melanomas. CONCLUSIONS: This CM cohort is composed of 83.3% in-situ melanoma and 16.7% invasive melanoma. Both patients had a higher percentage of SPM with clinical nevus-like morphology (84.5%), global dermoscopic pattern of asymmetric multiple component (60.3%) and located on the lower limbs (46.6%). When RCM was performed prior to excision, 81% of SPM had features suggestive of malignancy. As well, invasive melanomas were more frequent in the lower limbs (40%). In the multivariate model, for the two high-risk patients studied, the chance of a not associated with nevus ("de novo") invasive SPM diagnosis is 25 times greater than the chance of a diagnosis of a nevus-associated invasive SPM.

A general class of promotion time cure rate models with a new biological interpretation.

Over the last decades, the challenges in survival models have been changing considerably and full probabilistic modeling is crucial in many medical applications. Motivated from a new biological interpretation of cancer metastasis, we introduce a general method for obtaining more flexible cure rate models. The proposal model extended the promotion time cure rate model. Furthermore, it includes several well-known models as special cases and defines many new special models. We derive several properties of the hazard function for the proposed model and establish mathematical relationships with the promotion time cure rate model. We consider a frequentist approach to perform inferences, and the maximum likelihood method is employed to estimate the model parameters. Simulation studies are conducted to evaluate its performance with a discussion of the obtained results. A real dataset from population-based study of incident cases of melanoma diagnosed in the state of São Paulo, Brazil, is discussed in detail.

Manejo de defeitos complexos do couro cabeludo após excisão de tumores malignos / Management of complex scalp defects after excision of malignant tumors

Introdução: A reconstrução do couro cabeludo após a ressecção oncológica continua sendo um desafio para o cirurgião, especialmente considerando a incidência crescente de câncer de pele entre pacientes idosos. A matriz dérmica (MD) é um grupo heterogêneo de materiais de cobertura de feridas que auxiliam no fechamento da ferida e substituem algumas das funções da pele, temporária ou permanentemente. Pacientes com maior risco cirúrgico podem se beneficiar do uso de MD, que ajuda a gerar uma nova derme, oferecendo grandes melhorias na cobertura de defeitos complexos e extensos. Métodos: É um trabalho retrospectivo com análise de prontuário e relato de dois casos de pacientes do A.C.Camargo Cancer Center-SP, Brasil. Resultados: Relatamos dois casos de defeitos complexos e extensos de couro cabeludo em um centro único usando MD associada a enxerto cutâneo e terapia de pressão negativa (TPN) na cirurgia reconstrutiva após ressecção de neoplasia maligna da pele com resultados funcionais e estético satisfatório. Conclusões: As lesões extensas do couro cabeludo são um desafio na prática clínica e um tratamento multidisciplinar é fundamental. Os resultados obtidos indicam que a MD associada com a enxertia de pele parcial e com a TPN tem enorme potencial para aumentar as opções terapêuticas disponíveis para o cirurgião e possivelmente beneficiando os pacientes, especialmente aqueles que não têm condições clínicas para uma cirurgia extensa de cobertura com retalho microcirúrgico.

Introduction: Scalp reconstruction after cancer resection remains a challenge for surgeons, especially considering the increasing incidence of skin cancer among elderly patients. Dermal matrix (DM) is a heterogeneous group of wound covering materials that aid in wound closure and replace some of the skins functions, either temporarily or permanently. Patients at higher surgical risk can benefit from the use of DM, which help to generate a new dermis, offering great improvements in coverage of complex and extensive defects Methods: It is a retrospective study with analysis of medical records and report of two cases of patients at the A.C.Camargo Cancer Center-SP, Brazil. Results: We report two cases of complex and extensive scalp defects at a single center using DM associated with skin grafting and negative pressure therapy (NPT) in reconstructive surgery after resection of malignant skin neoplasm with satisfactory functional and esthetic results. Conclusions: Extensive lesions of the scalp are a challenge in clinical practice and a multidisciplinary treatment is essential. The results obtained indicate that DM associated with partial skin grafting and NPT have enormous potential to increase the therapeutic options available to the surgeon and possibly benefit patients, especially those who do not have the clinical conditions for extensive coverage surgery with microsurgical flap.

A phase 2 study of first-line nivolumab in patients with locally advanced or metastatic cutaneous squamous-cell carcinoma.

BACKGROUND: Cutaneous squamous-cell carcinoma (CSCC) is among the most frequent malignancies worldwide. For those not amenable to treatment with curative intent, immune checkpoint inhibition (ICI) with anti-programmed death receptor 1 (PD-1) antibodies has emerged as a novel therapeutic option. In this study, the authors sought to investigate the activity of the anti-PD-1 agent nivolumab in patients with advanced CSCC (aCSCC). METHODS: CA209-9JC was an open-label, single-arm, phase 2 study to evaluate the safety and/or efficacy of nivolumab in systemic treatment-naive patients with aCSCC. Nivolumab (3 mg/kg) was administered every 2 weeks until disease progression, unacceptable toxicity, or 12 months of treatment. The primary end point was the best objective response rate (BORR) as per RECIST 1.1 criteria. Secondary end points included safety, progression-free survival (PFS), and overall survival (OS). RESULTS: Twenty-four patients with aCSCC were enrolled with a median age of 74 years (range, 48-93). Among the 24 patients evaluable for response, the BORR was 58.3% (14/24); there were no complete responses. With a median follow-up of 17.6 months, median duration of response has not been reached, and the estimated median PFS and OS were 12.7 and 20.7 months, respectively. Prior exposure to radiotherapy was associated with worse outcomes (p = .035, univariate analysis). Treatment-related adverse events of any grade and grade ≥ 3 occurred in 21 (87.5%) and six (25%) patients, respectively, and one patient discontinued nivolumab due to toxicities. CONCLUSIONS: Nivolumab resulted in robust antitumor activity, sustained responses, and good tolerability in systemic treatment-naive patients with aCSCC. These data provide further evidence to support the use of ICI as the standard treatment of aCSCC.

Intraoperative assessment of surgical margins using ‟en face" frozen sections in the management of cutaneous carcinomas

Abstract Background: Basal cell and squamous cell carcinomas (BCC and SCC) are the most common types of cancer worldwide. Intraoperative assessment of surgical margins by frozen section has been widely used to ensure disease-free margins. The intraoperative ‟en face" freezing technique evaluates all peripheral and deep margins. Objective: To report the results of the ‟en face" freezing technique in relation to tumor recurrence and agreement with paraffin-embedded tissue examination. Methods: Retrospective analysis of patients undergoing surgical excision of BCC and SCC at the A. C. Camargo Cancer Center, Brazil. Results: This study included 542 skin carcinomas, which were excised from 397 patients. A total of 201 male patients (50.6%), and 196 female patients (49.4%) were assessed, whose mean age was 64 years. The tumors were mostly located on the head and neck region (87.8%). BCC corresponded to 79.7% of the cases. The mean follow-up was 38 months. Tumor relapse occurred in 0.86% of the primary tumors and 3.7% of recurrent tumors. The result of the intraoperative ‟en face" frozen section evaluation was in agreement with the final result of the anatomopathological examination (paraffin test) in 98% of the lesions. Study limitations: Not having a minimum follow-up time of 5 years for all patients. Conclusion: The ‟en face" freezing technique shows low tumor relapse, being reliable and safe to guarantee negative surgical margins of the tumor.

Intraoperative assessment of surgical margins using "en face" frozen sections in the management of cutaneous carcinomas.

BACKGROUND: Basal cell and squamous cell carcinomas (BCC and SCC) are the most common types of cancer worldwide. Intraoperative assessment of surgical margins by frozen section has been widely used to ensure disease-free margins. The intraoperative "en face" freezing technique evaluates all peripheral and deep margins. OBJECTIVE: To report the results of the "en face" freezing technique in relation to tumor recurrence and agreement with paraffin-embedded tissue examination. METHODS: Retrospective analysis of patients undergoing surgical excision of BCC and SCC at the A. C. Camargo Cancer Center, Brazil. RESULTS: This study included 542 skin carcinomas, which were excised from 397 patients. A total of 201 male patients (50.6%), and 196 female patients (49.4%) were assessed, whose mean age was 64 years. The tumors were mostly located on the head and neck region (87.8%). BCC corresponded to 79.7% of the cases. The mean follow-up was 38 months. Tumor relapse occurred in 0.86% of the primary tumors and 3.7% of recurrent tumors. The result of the intraoperative "en face" frozen section evaluation was in agreement with the final result of the anatomopathological examination (paraffin test) in 98% of the lesions. STUDY LIMITATIONS: Not having a minimum follow-up time of 5 years for all patients. CONCLUSION: The "en face" freezing technique shows low tumor relapse, being reliable and safe to guarantee negative surgical margins of the tumor.

Melanoma with peripheral globules: Clinical and dermatoscopic features.

BACKGROUND: The morphology and biology of nevi with peripheral globules are well known, whereas those of melanomas with peripheral globules remain unclear. OBJECTIVE: Comparing the dermatoscopic characteristics of nevi and melanomas with peripheral globules. METHODS: A total of 401 melanocytic lesions with peripheral globules were included in this retrospective study. Dermatoscopic patterns and structures, including those of peripheral globules, were evaluated. A generalized estimating equation model with a binomial distribution dependent variable and logit link function was fitted to the dataset to identify features with the highest odds of differentiating melanoma from nevi. RESULTS: Of the 401 lesions, 179 (44.64%) were excised, 41 (10.22%) of which were melanomas. Melanomas were most common in the lower extremities (P < .01), with a disorganized pattern, whereas melanocytic nevi were most common on the trunk, with an organized pattern. In addition, the presence of blotches, atypical dots and globules, or atypical vessels was associated with melanomas (P < .01). LIMITATIONS: The retrospective design of the study may have caused an inclusion bias. CONCLUSION: Melanocytic lesions displaying peripheral globules are at the greatest risk of melanoma if located on the lower extremity and if lesions reveal any of the following structures: blotch, atypical dots and globules, or atypical vessels.

Management of In-Transit Metastases.

PURPOSE OF REVIEW: The purpose of this study is to discuss the current knowledge and future perspectives regarding the treatment options for in-transit metastases (ITM), along with the optimal algorithms for patients presenting with this adverse manifestation of melanoma. RECENT FINDINGS: In addition to procedures historically accepted for the management of ITM, encompassing surgery and regional techniques, novel medications in the form of immune checkpoint inhibitors (ICI) and targeted therapies now represent standard options, allowing for the possibility of combined approaches, with an expanding role of systemic therapies. Melanoma in-transit metastases consist of intralymphatic neoplastic implants distributed between the primary site and the regional nodal basin, within the subepidermal and dermal lymphatics. Distinct risk factors may influence the development of ITM, and the clinical presentation can be highly heterogeneous, enhancing the complexity of the management of ITM. Surgical resection, when feasible, continues to represent a standard approach for patients with curative intent. Patients with extensive or unresectable disease may also benefit from regional approaches that include isolated limb perfusion or infusion, electrochemotherapy, and a wide variety of intralesional therapies. Over the past decade, regimens with ICI and BRAF/MEK inhibitors dramatically expanded the benefit of systemic treatments for patients with melanoma, both in the adjuvant setting and for those with advanced disease, and the combination of these modalities with regional treatments, as well as neoadjuvant approaches, may represent the future for the treatment of patients with ITM.

The Clinical Utility of Neuron-Specific Enolase (NSE) Serum Levels as a Biomarker for Merkel Cell Carcinoma (MCC).

BACKGROUND: No adequate biomarker for Merkel cell carcinoma (MCC) has been identified. Serum neuron-specific enolase (NSE) has been tested and is commonly used as a biomarker for several other small cell malignancies. However, the role of NSE in MCC is still unclear. The purpose of this study was to investigate the role of NSE as a biomarker in MCC. METHODS: A prospective cohort of MCC patients was analyzed using Kaplan-Meier curves with log-rank test, ROC curves, Cox regression, and mixed models. A separate evaluation was performed for patients treated with immunotherapy. RESULTS: Eighty-four patients were included [47 males, median age 71 years, stages I & II, III, and IV MCC in respectively 39 (46%), 42 (50%), and 4 (3%) patients at time of diagnosis] with 565 NSE samples (median 15; interquartile range 12.6-22 ng/ml). Baseline NSE had no association with prognosis. NSE correlated with extent of disease (P = 0.01) and increased with 15 ng/ml per class (no tumor load, localized MCC, regional or distant metastases, respectively). NSE was able to detect progression (AUC 0.89). A NSE of 18.2 ng/ml was considered the most optimal level for clinical use (sensitivity 91%, specificity 78%, PPV 48%, NPV 98%). During immunotherapy (N = 23; 248 NSE values), all complete responders (N = 10) had a normalized NSE (< 18.2 ng/ml), all partial responders (N = 5) had a decreasing NSE. In nonresponders (N = 8), all NSE levels remained elevated. CONCLUSIONS: NSE could be a valuable biomarker in MCC. NSE correlates with extent of disease; it is able to rule out progression and distinguishes responders from nonresponders during immunotherapy.

Development and validation of a Brazilian nomogram to assess sentinel node biopsy positivity in melanoma.

BACKGROUND: Although well-established, sentinel node biopsy (SNB) for melanoma is not free from controversies and sometimes it can be questionable if SNB should be considered even for patients who meet the criteria for the procedure. Mathematical tools such as nomograms can be helpful and give more precise answers for both clinicians and patients. We present a nomogram for SNB positivity that has been internally validated. METHODS: Retrospective analysis of patients who underwent SNB from 2000 to 2015 in a single institution. Single logistic regressions were used to identify variables that were associated to SNB positivity. All variables with a p value < 0.05 were included in the final model. Overall performance, calibration, and discriminatory power of the final multiple logistic regression model were all assessed. Internal validation of the multiple logistic regression model was performed via bootstrap analysis based on 1000 replications. RESULTS: Site of primary lesion, Breslow thickness, mitotic rate, histologic regression, lymphatic invasion, and Clark level were statistically related to SNB positivity. After internal validation, a good performance was observed as well as an adequate power of discrimination (area under the curve 0.751). CONCLUSIONS: We have presented a nomogram that can be helpful and easily used in daily practice for assessing SNB positivity.

Postoperative complications following simultaneous therapeutic and contralateral prophylactic nipple-sparing mastectomy: a retrospective study

Introduction: Nipple-Sparing Mastectomy (NSM) is increasingly indicated for therapeutic and prophylactic purposes due to better cosmetic results with nipple maintenance. Postoperative complications have not been compared among patients who have undergone simultaneous therapeutic and contralateral prophylactic NSM. The aim of the present study was to evaluate the incidence and risk factors for postoperative complications in bilateral/unilateral NSMs, and therapeutic and/or prophylactic NSMs. Methods: Retrospective study of patients who underwent NSM between 2007 and 2017 at A.C. Camargo Cancer Center. Results: Among 290 patients, 367 NSMs were performed, 64 simultaneous therapeutic and contralateral prophylactic NSM. The latter were associated with more postoperative complications (OR=3.42; p=0.002), mainly skin flap necrosis (OR=3.79; p=0.004), hematoma (OR=7.1; p=0.002), wound infection (OR=3.45; p=0.012), and nipple-areola complex (NAC) loss (OR=9.63; p=0.003). Of the 367 NSMs, 213 were unilateral NSMs, which were associated with lower rates of postoperative complications (OR=0.44; p=0.003), especially skin flap necrosis (OR=0.32; p=0.001), hematoma (OR=0.29; p=0.008), wound infection (OR=0.22; p=0.0001), and reoperation (OR=0.38; p=0.008). Obesity was related to more postoperative complications (OR=2.55; p=0.01), mainly hematoma (OR=3.54; p=0.016), reoperation (OR=2.68; p=0.023), and NAC loss (OR=3.54; p=0.016). Patients' age (p=0.169), their smoking status (p=0.138), breast ptosis (0.189), previous chest radiotherapy (p 1), or previous breast surgery (p=0.338) were not related to higher chances of postoperative complications. Conclusions: Results suggest that performing therapeutic and contralateral prophylactic NSM as separated procedures may represent a good strategy for minimizing postoperative complications.

The Role of Radiation Therapy as an Adjuvant Treatment in Nodal Metastasis of Malignant Chondroid Syringoma.

Malignant chondroid syringomas (MCSs) are extremely rare and aggressive skin tumors, and wide surgical excision is the main treatment. They can progress with local recurrence and nodal and distant metastasis. The role of radiotherapy is uncertain, but may enhance local control after surgical approach. We report a case of a 60-year-old female with this disease that, four years after surgical resection, presented with nodal metastasis and was managed with surgery and adjuvant radiotherapy.

How does the mitotic index impact patients with T1 melanoma? Comparison between the 7th and 8th edition of the American Joint Committee on Cancer melanoma staging system

Abstract Background: The mitotic index is no longer used to classify T1 melanoma patients into T1a and T1b, so it should not be used to indicate sentinel node biopsy in these patients. Objectives: To evaluate patients with T1 melanoma who underwent sentinel lymph node biopsy and to compare those who were classified as T1a with those classified T1b, according to the 7th and 8th Edition of the melanoma staging system, regarding a positive biopsy result. The authors also aimed to assess whether there is any difference in the results in both staging systems. Material and methods: This was a retrospective analysis of 1213 patients who underwent sentinel lymph node biopsy for melanoma, from 2000 to 2015, in a single institution. Results: Of 399 patients with thin melanomas, 27 (6.7%) presented positive sentinel lymph nodes; there was no difference in positivity for sentinel node biopsy when comparing T1a vs. T1b in both staging systems. Furthermore, the clinical results were also similar between the two groups. However, in the complete cohort analysis, the mitotic index was associated with positivity for sentinel lymph node biopsy (p < 0.0001), positivity for non-sentinel lymph node (p < 0.0001), recurrence-free survival (p < 0.0001), and specific melanoma survival (p = 0.023). Study limitation: Unicentric study. Conclusion: The mitotic index was shown to be a very important prognostic factor in the present study, but it was not observed in patients classified as T1. The mitotic index should no longer be used as the only reason to refer sentinel lymph node biopsy in patients with thin melanoma.

How does the mitotic index impact patients with T1 melanoma? Comparison between the 7th and 8th edition of the American Joint Committee on Cancer melanoma staging system.

BACKGROUND: The mitotic index is no longer used to classify T1 melanoma patients into T1a and T1b, so it should not be used to indicate sentinel node biopsy in these patients. OBJECTIVES: To evaluate patients with T1 melanoma who underwent sentinel lymph node biopsy and to compare those who were classified as T1a with those classified T1b, according to the 7th and 8th Edition of the melanoma staging system, regarding a positive biopsy result. The authors also aimed to assess whether there is any difference in the results in both staging systems. MATERIAL AND METHODS: This was a retrospective analysis of 1213 patients who underwent sentinel lymph node biopsy for melanoma, from 2000 to 2015, in a single institution. RESULTS: Of 399 patients with thin melanomas, 27 (6.7%) presented positive sentinel lymph nodes; there was no difference in positivity for sentinel node biopsy when comparing T1a vs. T1b in both staging systems. Furthermore, the clinical results were also similar between the two groups. However, in the complete cohort analysis, the mitotic index was associated with positivity for sentinel lymph node biopsy (p < 0.0001), positivity for non-sentinel lymph node (p < 0.0001), recurrence-free survival (p < 0.0001), and specific melanoma survival (p = 0.023). STUDY LIMITATION: Unicentric study. CONCLUSION: The mitotic index was shown to be a very important prognostic factor in the present study, but it was not observed in patients classified as T1. The mitotic index should no longer be used as the only reason to refer sentinel lymph node biopsy in patients with thin melanoma.

Sentinel Node Status is the Most Important Prognostic Information for Clinical Stage IIB and IIC Melanoma Patients.

BACKGROUND: Sentinel node biopsy (SNB) for melanoma patients has been questioned. We aimed to study high-risk stage II melanoma patients who underwent SNB to determine what the prognostic factors regarding recurrence and mortality were, and evaluate how relevant SNB status is in this scenario. METHODS: This was a retrospective analysis of clinical stage IIB/IIC melanoma patients who underwent SNB from 2000 to 2015 in a single institution. Prognostic factors related to distant recurrence-free survival (DRFS) and melanoma-specific survival (MSS) were assessed from multiple Cox regression. Relevant variables were used to create risk predictor nomograms for DRFS and MSS. RESULTS: From 1213 SNB, 259 were performed for clinical stage IIB/IIC melanoma patients. SNB status was the most important variable for both endpoints. Patients with positive SNB presented median DRFS of 35.73 months (95% CI 21.38-50.08, SE 7.32) and median MSS of 66.4 months (95% CI 29.76-103.03, SE 18.69), meanwhile both median DRFS and MSS were not achieved for those with negative SNB (logrank < 0.0001). Both nomograms have been internally validated and presented adequate calibration (C-index was 0.734 for DRFS and 0.718 for MSS). CONCLUSIONS: SNB status was the most important risk factor in our cohort of clinical stage IIB and IIC patients and, in conjunction with well-established primary tumor characteristics, should not be abandoned. Their use in prognosis for these patients remains extremely useful for daily practice.